Zhiqiang An, Ph.D.
Professor, Texas Therapeutics InstituteZhiqiang.An@uth.tmc.edu
Dr. An received his Ph.D. from the University of Kentucky, Lexington, followed by postdoctoral training at the University of Wisconsin-Madison. Before joining the IMM, he was Chief Scientific Officer at Epitomics, Inc., a biotech company dedicated to developing monoclonal antibodies for research, diagnostic and therapeutic applications. Previously, he was Director of Biologics Research, Merck Research Laboratories. In his tenure at Merck, Dr. An played a major role in the creation of Merck's biologics research department including the establishment of the antibody technology platform and pipeline. Dr. An started his biotech/pharmaceutical career at Millennium Pharmaceuticals where he focused on biocombinatorial natural products drug discovery using microbial molecular genetics and engineering approaches.
Dr. An’s research team will focus on the cancer drug resistance mechanisms in the HER/ErbB signaling pathways using monoclonal antibodies as platform technology. The team will explore mechanisms of cancer drug resistance and discover/develop antibodies for potential diagnostic and therapeutic applications. Drug resistance is often a limiting factor for clinical efficacy of existing cancer therapies. Growing evidence indicates that HER3/ErbB3 plays an important role in the overall HER signaling pathway and in drug resistance. Currently, there are no HER3-targeting therapies and clinical development of HER3 therapeutics is limited. To better understand HER3 biology and its role in drug resistance, we will generate a unique panel of HER3 neutralizing monoclonal antibodies targeting all functional epitopes by direct antibody cloning from circulating plasma B cells from rabbit and mouse immunized with rationally designed HER3 antigens. The results from the study will not only shed light on the molecular basis of physiological and pathophysiological states of the HER signaling cascade, but also help to illustrate a system approach for cancer treatment. Antibodies discovered in this program will be evaluated in preclinical disease models and developed as cancer diagnostics and therapeutics.
Selected peer-reviewed publications
An Z, Mei B, Yuan WM, Leong SA. The distal GATA sequences of the sid1 promoter of Ustilago maydis mediate iron repression and interact directly with Urbs1, a transcription repressor and a member of the GATA family of transcription factors. EMBO J 1997;16:1742-1750.
An Z, Zhao Q, McEvoy J, Yuan WM, Markley JL, Leong SA. The second finger of Urbs1 is required for iron-mediated repression of sid1 of Ustilago maydis. Proc. Natl. Acad. Sci. USA 1997; 94:5882-5887.
Ferreira AVB, An Z, Metzenberg RL, Glass NL. Characterization of mat A-2, mat A-3 and DmatA mating-type mutants of Neurospora crassa. Genetics 1998;148:1069-1079.
Zhang A, Lu P, Dahl-Roshak A, Paress P, Kennedy S, Tkacz J, An Z. Efficient Disruption of a Polyketide Synthase Gene (pks1) Required for Melanin Synthesis Through Agrobacterium-mediated Transformation of Glarea lozoyensis. Mol Genet Genomics 2003; 268:645-655.
Lu P, Zhang A, Dennis LM, Dahl-Roshak AM, Xia YQ, Arison B, An Z, Tkacz JS.. A Gene (pks2) Encoding a Putative6-Methylsalicylic Acid Synthase from Glarea lozoyensis. Mol Genet Genomics 2005; 273:207-216.
Miller DM, Geleziunas R, Bianchi E, Lennard S, Hrin R, Zhang H, Lu M, An Z, Ingallinella P, Finotto M, Mattu M, Finnefrock A, Bramhill D, Cook J, Eckert D, Hampton R, Patel M, Jarantow S, Joyce J, Ciliberto G, Cortese R, Lu P, Strohl W, Schleif W, McElhaugh M, Lane S, Lloyd C, Lowe D, Osbourn J, Vaughan T, Emini E, Barbato G, Kim PS, Hazuda DJ, Shiver J, Pessi A. . A human monoclonal antibody neutralizes diverse HIV-1 isolates by binding to a critical gp41 epitope. Proc. Natl. Acad. Sci. USA 2005; 102(41):14759-64.
Su B, Hrin R, Harvey B, Wang YJ, Ernst R, Hampton R, Miller M, Strohl W, An Z, Montgomery D. Automated high-throughput purification of antibody fragments to facilitate evaluation in functional and kinetic based assays. J Immunol Methods 2007; 322:94-103.
Yang Y, Yang E, An Z, Liu X. Evolution of nematode-trapping cells of predatory fungi of the Orbiliaceae (Ascomycotina): evidence from ribosomal DNA and multiprotein nucleotide sequences. Proc. Natl. Acad. Sci. USA 2007; 104:8379-8384.
Ireland C, Peekhaus N, Lu P, Sangari R, Zhang A, Masurekar P, An Z. The tryptophan synthetase gene TRP1 of Nodulisporium sp.: molecular characterization and its relation to nodulisporic acid A production. Appl Genet Mol Biotechnol 2008; 79(3):451-459.
Hrin R, Montgomery DL, Wang F, Condra JH, An Z, Strohl WR, Bianchi E, Pessi A, Joyce JG, Miller MD, Wang YJ. in vitro synergy between peptides or neutralizing antibodies targeting the N- and C-terminal heptad repeats of HIV-1 gp41. AIDS Res Hum Retrov 2008; 24(12) 1537-1544.
Chin CN, Yang QD, Liu F, Ho T, Ellsworth K, Fischer P, Natasha T, Ireland C, Lu P, Li C, Wang IM, Strohl WR, Berger JP, An Z, Zhang B, Jiang G. Evidence that inhibition of insulin receptor signaling activity by PC-1/ENPP1 is dependent on its enzyme activity. Eur J Pharmacol 2009; 606:17-24.
Zhou HH, Chin CN, Wu M, Nia W, Quan S, Liu F, Dallas-Yang Q, Ellsworth K, Ho T, Zhang A, Natasha T, Li J, Chapmana K, Strohl W, Li C, Wang IM, Berger J, An Z, Zhang BB, Jiang G. Suppression of PC-1/ENPP-1 expression improves insulin sensitivity in vitro and in vivo. Eur J Pharmacol 2009; 616:346-352.
Montgomery DL, Wang YJ, Hrin R, Luftig M, Su B, Miller MD, Wang F, Haytko P, Huang L, Vitelli S, Condra J, Liu X, Hampton R, Carfi A, Pessi A, Bianchi E, Finnefrock A, Joyce J, Lowe D, Geleziunas R, Bramhill D, King VM, Strohl W, An Z. Affinity maturation and characterization of a human monoclonal antibody against HIV-1 gp41. mAbs 2009, 1(5):462-474.
An Z, Forrest G, Moore R, Cukan M, Haytko P, Huang L, Vitelli S, Zhao JX, Lu P, Hua J, Gibson CR, Harvey B, Montgomery D, Zaller D, Wang F, Strohl WR. 2009. IgG2M4, an engineered antibody isotype with reduced Fc function. mAbs 1(6):572 - 579.
Zhang Y, Liu X, An Z, Wang M, Guo Y, Zhang S. 2009. Genetic diversity of Ophiocordyceps sinensis, a medicinal fungus endemic to the Tibetan Plateau: Implications for its evolution and conservation. BMC Evol Biol 9:290(1-7).
Yu Y, Lee P, Ke Y, Zhang Y, Yu Q, Lee J, Li M, Song J, Chen J, Dai J, Couto FJRD, An Z*, Zhu Z, Yu G. 2010. A humanized anti-VEGF rabbit monoclonal antibody inhibits angiogenesis and blocks tumor growth in xenograft models. Plos One 5(2):e9072 (1-12).
An Z. 2005. Handbook of Industrial Mycology, Editor, Marcel Dekker, p763, New York, NY.
An Z. 2009. Therapeutic Monoclonal Antibodies: from Bench to Clinic, Editor, John Wiley and Sons, p889, Hoboken, NJ.